The significance of Epstein Barr Virus (EBV) &amp; DNA Topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC)

Shamaa, Ali; Zyada, Manal M.; Wagner, Mathias; Awad, Sally; Osman, Mohamed; Azeem, Ali A Abdel

doi:10.1186/1746-1596-3-45

Cited by 39 publications

(38 citation statements)

References 63 publications

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“…Also, in a study by Kis et al on prevalence of EBV, none of the OSCC samples tested immunohistochemically were found to be LMP‐1 positive . Talacko et al using in situ hybridization demonstrated that EBV DNA was not present in the neoplastic cells of OSCC(Table ) .…”

Section: Discussionmentioning

confidence: 99%

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Expression of Epstein–Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco‐chewing population

Reddy

Sharma

Mysorekar

2016

J Oral Pathology Medicine

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Section: Discussionmentioning

confidence: 99%

“…This result implies a possible direct relation between EBV infection and epithelial dysplasia as well as OSCC. EBV expression was increased as tumor differentiation decreased . Mao and Smith and Horiuchi et al showed that 35% and 33.3% of OSCC cases examined were infected with EBV.…”

Section: Discussionmentioning

confidence: 99%

Expression of Epstein–Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco‐chewing population

Reddy

Sharma

Mysorekar

2016

J Oral Pathology Medicine

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“…In malignant cells, overexpression of TOP2A protein might reflect not only the proliferative advantage of these cells, but also qualitative alterations caused by malignant transformation and dedifferentiation [12]. The IHC method for in situ determination of TOP2A has been extensively validated and shown to reflect closely the exact enzyme activity in formalin-fixed paraffin-embedded human tissues, leading to the prognostic and predictive importance of this test in other neoplasms [16]. …”

Section: Discussionmentioning

confidence: 99%

Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer

et al. 2013

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BackgroundTOP2A encodes for topoisomerase IIα, a nuclear enzyme that controls DNA topological structure and cell cycle progression. This enzyme is a marker of cell proliferation in normal and neoplastic tissues; however, little information is available about its expression in prostate cancer (PCa).MethodsImmunohistochemistry (IHC) was automated using mouse monoclonal antibody against TOP2A (clone SWT3D1; DAKO, Carpenteria, CA, USA) at dilution 1:800 and Flex Plus detection system in autostainer 48Ultra (DAKO). FISH was performed using TOP2A (17q21)/ CEP17 probe kit (Kreateck Biotechnology, San Diego, CA, USA). Biochemical and pathological data from 193 patients with PCa were retrieved for the analysis, whose significance was considered when p < 0.05. Also, fractal analysis was performed in a subset of 20 randomly selected cases.ResultsTOP2A protein expression correlated with higher Gleason scores and higher levels of preoperative PSA (p = 0.018 and p = 0.011). Patients with higher levels of TOP2A presented shorter biochemical recurrence-free survival (BRFS) (p = 0.001). In multivariate analysis, we found that TOP2A remained an independent prognostic factor of BRFS, with a relative risk of 1.98 (p = 0.001; 95% CI, 1.338–2.93); thus, cases that expressed high levels of this enzyme had a shorter BRFS compared with TOP2A-negative or TOP2A-low cases. No alterations in TOP2A gene status nor correlation between FISH and IHC results were observed. Concerning fractal analysis, patients who expressed higher levels of TOP2A have angiolymphatic invasion and presented higher Gleason scores (p = 0.033 and p = 0.025, respectively). Also, patients with higher expression of TOP2A presented shorter BRFS (p = 0.001).ConclusionsThis is the first study to perform TOP2A protein and gene digital assessment and fractal analysis in association with BRFS in a large series of PCa. Also, we show that TOP2A gene copy number alterations are not observed in this type of tumor. So, higher protein expression of TOP2A is not related to gene amplification in PCa. Furthermore, TOP2A protein assessment has prognostic importance and, due to its relation with poor outcome, TOP2A IHC evaluation in the biopsy can represent an important tool for selecting the most suitable surgical and clinical approach for patients with PCa.

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“…TopoII alpha is an enzyme with an important role in DNA topology, repair and replication, coded by a single copy gene on the locus q21of chromosome 17 [8,9]. It is a cell-cycle-related protein, expressed in normal as well as neoplastic cells in the S, G2 and M phase [8,10,11]. …”

Section: Introductionmentioning

confidence: 99%

P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas

et al. 2013

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BackgroundWe investigated the immunohistochemical expression of p53, MAPK, topoisomerase II alpha (topoII alpha) and Ki67 in ovarian serous carcinomas (OSCs) along with mutational analysis for KRAS and BRAF.MethodsEighty one cases of OSCs were reviewed and examined immunohistochemically using antibodies against p53, MAPK, topoII alpha and Ki67. Staining was evaluated as a percentage of immunopositive cells with cut-off levels at 10% for p53 and topoII alpha, and 5% for MAPK. The Ki67 immunoexpression was assessed by means of Olympus Image Analysis System as a percentage of immunopositive cells in 1000 tumor cells. KRAS and BRAF mutational analysis was performed on 73 available microdissected samples.ResultsOf 81 cases of OSCs 13.6% were of low-grade and 86.4% were of high-grade morphology. In the high-grade group there was a significantly higher immunoexpression of p53 (P < 0.001) and topoII alpha (P = 0.001), with Ki67 median 56.5 vs. 19 in low-grade group (P < 0.001). The difference in immunoexpression of active MAPK between low- and high-grade group was also significant (P = 0.003). MAPK positive immunostaining was detected in 63.6% of low-grade vs. 17.1% of high-grade OSCs. The frequency of KRAS mutation was significantly higher in low-grade as compared to high-grade group (P = 0.006). None of the samples had BRAF mutation. In addition, we detected positive MAPK immunoexpression in 13/59 samples with wild-type KRAS, suggesting that activation of MAPK pathway is not ultimately related either to KRAS or BRAF mutation. Seven morphologically high-grade samples (11.7%) showed both KRAS mutation and p53 immunopositivity.ConclusionsAlthough this study is limited by its humble number of low-grade samples, our data fit the proposed dualistic pathway of ovarian carcinogenesis. Mutational analysis for KRAS and BRAF discloses some possible interactions between different tumorigenic pathways of low- and high-grade carcinomas. Immunohistochemical staining for MAPK was not sufficiently sensitive, nor specific, to precisely predict the KRAS mutation. However, it appears to be quite reliable in ruling out a KRAS mutation if the staining is negative.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9283563368804632ZusammenfassungHintergrundWir untersuchten die Immunohistochemische Expression der p53, MAPK, topoisomerase II alpha (topoII alpha) und Ki67 in Ovarialkarzinomen (OSCs) anbei mit Mutationsanalyse für KRAS und BRAF.Methode81 OSCs Fälle wurden analysiert und Immunohistochemisch untersucht mit Antikörper gegen p53, MAPK, topoII alpha und Ki67. Die Färbung war ausgewertet als der Prozent von immunopositiven Zellen mit den “cut-of” Niveau an 10% für p53 und topoII alpha und 5% für MAPK. Die Ki67 Expression war bewertet mittels Olympus Image Analysis System als der Prozent von immunopositiven Zellen in 1000 Tumorzellen. KRAS and BRAF Mutationsanalyse wurde in 73 verfügbaren microdissections Stichproben aufgeführt.ErgebnisseVon 81 OSCs Fälle 13.6% zeigte “lo...

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The significance of Epstein Barr Virus (EBV) & DNA Topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC)

Cited by 39 publications

References 63 publications

Expression of Epstein–Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco‐chewing population

Expression of Epstein–Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco‐chewing population

Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer

P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas

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